• Genomics & Informatics
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• v.12 no.4
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• pp.276-282
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• 2014

The disease tuberculosis, caused by Mycobacterium tuberculosis (MTB), remains a major cause of morbidity and mortality in developing countries. The evolution of drug-resistant tuberculosis causes a foremost threat to global health. Most drug-resistant MTB clinical strains are showing resistance to isoniazid and rifampicin (RIF), the frontline anti-tuberculosis drugs. Mutation in rpoB, the beta subunit of DNA-directed RNA polymerase of MTB, is reported to be a major cause of RIF resistance. Amongst mutations in the well-defined 81-base-pair central region of the rpoB gene, mutation at codon 450 (S450L) and 445 (H445Y) is mainly associated with RIF resistance. In this study, we modeled two resistant mutants of rpoB (S450L and H445Y) using Modeller9v10 and performed a docking analysis with RIF using AutoDock4.2 and compared the docking results of these mutants with the wild-type rpoB. The docking results revealed that RIF more effectively inhibited the wild-type rpoB with low binding energy than rpoB mutants. The rpoB mutants interacted with RIF with positive binding energy, revealing the incapableness of RIF inhibition and thus showing resistance. Subsequently, this was verified by molecular dynamics simulations. This in silico evidence may help us understand RIF resistance in rpoB mutant strains.

• Proceedings of the IEEK Conference
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• 2009.05a
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• pp.135-137
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• 2009

Mathematical models for describing the Human Immunodeficiency Virus(HIV) infection can be devised to better understand how the HIV causes Acquired Immune Deficiency Syndrome(AIDS). The HIV models can then be used to find clues to curing AIDS from a control theoretical point of view. Some models take Cytotoxic T Lymphocytes(CTL) response to HIV infection into account, and others consider mutants against the drugs. However, to the best of our knowledge, there has been no model developed, which describes CTL response and mutant HIV together. Hence we propose a unified model to consider both of these. On the basis of the resulting model, we also present a Model Predictive Control(MPC) scheme to find an optimal treatment strategy. The optimization is performed under the assumption that the Structured Treatment Interruption(STI) policy is employed.

• The Korean Journal of Mycology
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• v.24 no.2 s.77
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• pp.135-141
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• 1996

Auxotrophs and drug resistant mutants from the mycelia of Lentinus edodes were obtained by UV irradiation at survival rates of $0.024{\sim}2.45%$ and ethidium bromide (EtBr) enrichment after UV irradiation. The mutation rate was 0.40%, and back mutation rate was $4.81{\times}10^{-4}{\sim}8.46{\times}10^{-4}$. Various amino acid-, nucleic acid-, and vitamin-requiring auxotrophs were isolated. The concentrations of several fungicides, antibiotics and amino acid analogues inhibiting the growth of L. edodes were determined. The MIC values for cycloheximide, benomyl, and p-fluorophenylalanine were 2, 2000, and 1000 ug/ml respectively. Five p-fluorophenylalanine-resistant mutants and eight benomyl-resistant mutants were selected by UV irradiation.

• Molecules and Cells
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• v.25 no.1
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• pp.119-123
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• 2008

Pyrimidine antagonists including 5-Fluorouracil (5-FU) have been used in chemotherapy for cancer patients for over 40 years. 5-FU, especially, is a mainstay treatment for colorectal cancer. It is a pro-drug that is converted to the active drug via the nucleic acid biosynthetic pathway. The metabolites of 5-FU inhibit normal RNA and DNA function, and induce apoptosis of cancer cells. One of the major obstacles to successful chemotherapy is the resistance of cancer cells to anti-cancer drugs. Therefore, it is important to elucidate resistance mechanisms to improve the efficacy of chemotherapy. We have used C. elegans as a model system to investigate the mechanism of resistance to 5-FU, which induces germ cell death and inhibits larval development in C. elegans. We screened 5-FU resistant mutants no longer arrested as larvae by 5-FU. We obtained 18 mutants out of 72,000 F1 individuals screened, and mapped them into three complementation groups. We propose that C. elegans could be a useful model system for studying mechanisms of resistance to anti-cancer drugs.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.70.2-71
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• 2003

Quinolone resistance in Streptococcus pneumoniae is related to mutations in the DNA gyrase and topoisomerase IV genes. DW-286a displayed potent activity against S. pneumoniae C9211 (MIC, 0.015 ${\mu}$g/ml) compared with gemifloxacin (MIC, 0.06 ${\mu}$g/ml). This study was performed to analyze the ability of DW-286a to cause resistance development in S. pneumoniae and to establish whether DNA gyrase or topoisomerase IV is primary target. DW-286a resistant mutants of S. pneumoniae C9211 were generated by stepwise selection at increasing drug concentration. (omitted)

• Journal of Microbiology and Biotechnology
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• v.31 no.5
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• pp.645-658
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• 2021

Porins are essential for the viability of Gram-negative bacteria. They ensure the uptake of nutrients, can be involved in the maintenance of outer membrane integrity and define the antibiotic or drug resistance of organisms. The function and structure of porins in proteobacteria is well described, while their function in photoautotrophic cyanobacteria has not been systematically explored. We compared the domain architecture of nine putative porins in the filamentous cyanobacterium Anabaena sp. PCC 7120 and analyzed the seven candidates with predicted OprB-domain. Single recombinant mutants of the seven genes were created and their growth capacity under different conditions was analyzed. Most of the putative porins seem to be involved in the transport of salt and copper, as respective mutants were resistant to elevated concentrations of these substances. In turn, only the mutant of alr2231 was less sensitive to elevated zinc concentrations, while mutants of alr0834, alr4741 and all4499 were resistant to high manganese concentrations. Notably the mutant of alr4550 shows a high sensitivity against harmful compounds, which is indicative for a function related to the maintenance of outer membrane integrity. Moreover, the mutant of all5191 exhibited a phenotype which suggests either a higher nitrate demand or an inefficient nitrogen fixation. The dependency of porin membrane insertion on Omp85 proteins was tested exemplarily for Alr4550, and an enhanced aggregation of Alr4550 was observed in two omp85 mutants. The comparative analysis of porin mutants suggests that the proteins in parts perform distinct functions related to envelope integrity and solute uptake.

• YAKHAK HOEJI
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• v.24 no.1
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• pp.1-10
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• 1980

Viomycin inhibited polypeptide biosynthesis, initiation complex formation and translocation of peptidyl-tRNA on ribosomes derived from a sensitive strain of Mycobacterium smegmatis (R-15), but not significantly on ribosomes from viomycin-resistant mutants(R-31 and R-43). The inhibition of translocation was stronger than that of initiation complex formation in the sensitive strain. The binding of [$^{14}C$] tuberactinomycin O, a viomycin analog, to ribosomal particles was studied by Millipore filter method. The sensitive ribosome exhibited higher affinity for the antibiotic than the resistant ribosomes. The resistance was localized on the large ribosomal subunit in a mutant(R-31), and on the small subunit in another mutant(R-43). The binding of the drug to the sensitive ribosomal subunit was markedly reduced by combination with the resistant pair subunit, and the entire ribosome became resistant to the antibiotic.

• Journal of Life Science
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• v.15 no.2 s.69
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• pp.182-185
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• 2005

We used the IS1096 transposon to construct Mycobacterium bovis BCG mutants resistant to an antituberculosis drug PA-824 and isolated several different mutants. We identified the locations of the insertions and found that the insertions were at various sites including the genes for the PPE proteins. HPLC analyses of the extracts of these five PPE mutant cells showed that three mutants produced only F0, and intermediate for the synthetic pathway of coenzyme $F^{420}$, and the remaining two neither F0 nor $F^{420}$. These data suggest that the products of these PPE genes are somehow involved in the biosynthesis of the coenzyme $F^{420}$.

• Proceedings of the Korean Society of Plant Pathology Conference
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• 2003.10a
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• pp.117.1-117
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• 2003

Phytophthora blight, caused by P. capsici, is very important disease of pepper. Many fungicides to control of Phytophthora blight have been developed, but most of fungicides disappeared in short periods. Nowadays dimethomorph was known as one of the most effective to control of this disease. P. capsici isolates from pepper fields were collected and surveyed their growth in dimethomorph amended V8 medium in order to evaluate their fungicides resistance. The fungicide resistant isolates were not founded among them. Most of the sensitive isolates were inhibited perfectly in V8 medium amended with 10ppm dimethomorph. Mutants of P. capsici by dimethomorph, was grown very well in 250ppm. The difference of pathogenicity, colony morphology, drug response, RT-PCR results was identified between sensitive and resistance isolates. This study should be provided a basic information about the occurrence of dimethomorph resistant isolates and genetic changes in P. capsici population.

• The Transactions of The Korean Institute of Electrical Engineers
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• v.56 no.10
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• pp.1836-1843
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• 2007

In this paper, we study the NvBAT treatment for AIDS patients that is combined with PI rather than RTI, while the Previous results have been focused on the NvBAT in conjuction with RTI. To this end, we obtain a bifurcation diagram which shows a change in the equilibrium points, and in their stability properties as the PI drug effect is varied. Based on the bifurcation diagram, we show that the NvBAT can be combined with drug PI for the treatment of AIDS patients. Various computer simulation results are included, which show the superiority of the NvBAT with PI over that with RTI. Accordition to simulation result, the NvBAT combined with PI is able to keep virus load level lower than that combined with RTI, which is crucial to avoid the emergence of drug-resistant mutants. Moreover, it is shown that, for some AIDS patients, NvBAT with RTI cannot make patients into long term non-progressor, while NvBAT with PI can.